HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print August 21, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0403140v1 74/6/1094    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mytar, B. Articles by Zembala, M. Search for Related Content PubMed PubMed Citation Articles by Mytar, B. Articles by Zembala, M.

(Journal of Leukocyte Biology. 2003;74:1094-1101.)
© 2003 by Society for Leukocyte Biology

Tumor cell-induced deactivation of human monocytes

Boenna Mytar, Maria Wooszyn, Rafa Szatanek, Monika Baj-Krzyworzeka, Maciej Siedlar, Irena Ruggiero, Jerzy Wickiewicz and Marek Zembala¹

Department of Clinical Immunology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland

¹ Correspondence: Department of Clinical Immunology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663 Cracow, Poland. E-mail: mizembal{at}cyf-kr.edu.pl

Although blood monocytes exhibit significant cytotoxic activity against tumor cells, the function of tumor infiltrating macrophages (TIM) is depressed in cancer patients. This study addresses the question of how the antitumor response of human monocytes, assessed by production of cytokines (tumor necrosis factor , TNF; IL-10; IL-12p40) and cytotoxicity, is altered by exposure to cancer cells. Tumor cell-pre-exposed monocytes restimulated with tumor cells showed significantly decreased production of TNF, IL-12, increased IL-10 (mRNA and release) and inhibition of IL-1 receptor-associated kinase-1 (IRAK-1) expression. This down-regulation of cytokine production was selective, as the response of pre-exposed monocytes to lipopolysaccharide (LPS) was unaffected. Treatment of tumor cell-pre-exposed monocytes with hyaluronidase (HAase) improved their depressed production of TNF, while HAase-treated cancer cells did not cause monocyte dysfunction. The response of hyaluronan (HA)-pre-exposed monocytes to stimulation with tumor cells was also inhibited. Cytotoxic activity of monocytes pretreated with cancer cells was also decreased. This study shows that tumor cells selectively deactivate monocytes and suggests that tumor cell-derived HA by blocking CD44 on monocytes inhibits their antitumor response. These observations may provide some explanation for the depressed function of TIM in human malignancy.

Key Words: cytokines • hyaluronan • IRAK-1

This article has been cited by other articles:

				M. Stec, K. Weglarczyk, J. Baran, E. Zuba, B. Mytar, J. Pryjma, and M. Zembala Expansion and differentiation of CD14+CD16 and CD14++CD16+ human monocyte subsets from cord blood CD34+ hematopoietic progenitors J. Leukoc. Biol., September 1, 2007; 82(3): 594 - 602. [Abstract] [Full Text] [PDF]

				D.-M. Kuang, Y. Wu, N. Chen, J. Cheng, S.-M. Zhuang, and L. Zheng Tumor-derived hyaluronan induces formation of immunosuppressive macrophages through transient early activation of monocytes Blood, July 15, 2007; 110(2): 587 - 595. [Abstract] [Full Text] [PDF]

				C. del Fresno, K. Otero, L. Gomez-Garcia, M. C. Gonzalez-Leon, L. Soler-Ranger, P. Fuentes-Prior, P. Escoll, R. Baos, L. Caveda, F. Garcia, et al. Tumor Cells Deactivate Human Monocytes by Up-Regulating IL-1 Receptor Associated Kinase-M Expression via CD44 and TLR4 J. Immunol., March 1, 2005; 174(5): 3032 - 3040. [Abstract] [Full Text] [PDF]

				M. Siedlar, M. Frankenberger, E. Benkhart, T. Espevik, M. Quirling, K. Brand, M. Zembala, and L. Ziegler-Heitbrock Tolerance Induced by the Lipopeptide Pam3Cys Is Due to Ablation of IL-1R-Associated Kinase-1 J. Immunol., August 15, 2004; 173(4): 2736 - 2745. [Abstract] [Full Text] [PDF]